Combined use of serum ferritin and KL-6 levels as biomarkers for predicting COVID-19 severity

Hiromu Tanaka; Erika Toya; Shotaro Chubachi; Ho Namkoong; Takanori Asakura; Shuhei Azekawa; Shiro Otake; Kensuke Nakagawara; Takahiro Fukushima; Mayuko Watase; Kaori Sakurai; Katsunori Masaki; Hirofumi Kamata; Makoto Ishii; Naoki Hasegawa; Yukinori Okada; Ryuji Koike; Yuko Kitagawa; Akinori Kimura; Seiya Imoto; Satoru Miyano; Seishi Ogawa; Takanori Kanai; Koichi Fukunaga

doi:10.1016/j.resinv.2024.09.011

Combined use of serum ferritin and KL-6 levels as biomarkers for predicting COVID-19 severity

Respir Investig. 2024 Oct 3;62(6):1132-1136. doi: 10.1016/j.resinv.2024.09.011. Online ahead of print.

Authors

Hiromu Tanaka¹, Erika Toya¹, Shotaro Chubachi², Ho Namkoong³, Takanori Asakura⁴, Shuhei Azekawa¹, Shiro Otake¹, Kensuke Nakagawara¹, Takahiro Fukushima¹, Mayuko Watase¹, Kaori Sakurai¹, Katsunori Masaki¹, Hirofumi Kamata¹, Makoto Ishii⁵, Naoki Hasegawa³, Yukinori Okada⁶, Ryuji Koike⁷, Yuko Kitagawa⁸, Akinori Kimura⁹, Seiya Imoto¹⁰, Satoru Miyano¹¹, Seishi Ogawa¹², Takanori Kanai¹³, Koichi Fukunaga¹

Affiliations

¹ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
² Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. Electronic address: [email protected].
³ Department of Infectious Diseases, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
⁴ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Department of Clinical Medicine (Laboratory of Bioregulatory Medicine), Kitasato University School of Pharmacy, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan; Department of Respiratory Medicine, Kitasato University, Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
⁵ Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
⁶ Department of Statistical Genetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
⁷ Health Science Research and Development Center (HeRD), Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
⁸ Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
⁹ Institute of Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
¹⁰ Division of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, the University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-0071, Japan.
¹¹ M&D Data Science Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
¹² Department of Pathology and Tumor Biology, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
¹³ Division of Gastroenterology and Hepatology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

PMID: 39366121
DOI: 10.1016/j.resinv.2024.09.011

Abstract

Objectives: To assess the value of serum ferritin and Krebs von den Lungen-6 (KL-6) levels for predicting severe COVID-19 (death or requirement for invasive mechanical ventilation [IMV]/high-flow oxygen).

Methods: Data were analyzed on 2495 patients with COVID-19 from February 2020 to November 2022 using data from a nationwide COVID-19 database.

Results: Patients with high KL-6 and low ferritin levels were older with more comorbidities and higher mortality rates, whereas those with high ferritin and low KL-6 levels were younger, predominantly male, and more likely to need IMV. A high level of both markers was strongly associated with critical outcomes (adjusted odds ratio: 13.6, 95% confidence interval: 8.58-21.5). The combination of both markers had higher predictive value than either marker alone (area under the curve: 0.709, 0.745, and 0.781 for KL-6, ferritin, and KL-6 + ferritin, respectively).

Conclusions: The combination of both markers accurately predicted COVID-19 severity.

Keywords: Biomarkers; Prognosis; Pulmonary fibrosis; SARS-CoV-2.